Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model
Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model
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DOI：
10.1016/j.biomaterials.2013.04.059
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发表时间：
2013-10-01
期刊：
影响因子：
14
通讯作者：
Hoerstrup, Simon P.
中科院分区：
文献类型：
--
作者：
Weber, Benedikt;Dijkman, Petra E.;Hoerstrup, Simon P.
基于脱细胞异种或同种异体基质的心脏瓣膜组织工程已显示出良好的临床效果。然而，健康的同种供体瓣膜的可用性是有限的，并且异种材料与感染和免疫风险有关。为了解决这些局限性，可生物降解的合成材料已成功地用于在体外创建活的自体组织工程心脏瓣膜(TEHs)。由于这些经典的组织工程技术需要大量的基础设施和物流，我们最近引入了基于可生物降解的合成材料和血管衍生细胞的脱细胞TEHs(DTEHs)，并成功地创造了一种潜在的现成的引导组织再生的起始基质。在这里，我们在一个非人类灵长类动物模型中调查了这种dTEHs的宿主再种群能力，并进行了长达8周的跟踪。在微创进入原位肺位置后，dTEHs在8周的随访中显示出可移动的薄叶。此外，还检测到轻-中度瓣膜功能不全和相对的瓣叶缩短。然而，与脱细胞的人类天然心脏瓣膜控制-代表目前使用的同种移植物-dTEHs相比，dTEHs显示出显著的细胞重新繁殖。鉴于这种强大的原位重塑能力，这些结果表明，人类细胞来源的生物工程脱细胞材料是一种有前途的、具有临床意义的心脏瓣膜组织工程起始基质。通过提供同源的、非免疫原性的、现成的替代结构，这些生物材料可能最终克服目前使用的瓣膜置换的局限性。(C)2013爱思唯尔有限公司。保留所有权利。
Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissue-engineered heart valves (TEHVs) in vitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-the-shelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive delivery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control - representing currently used homografts - dTEHVs showed remarkable rapid cellular repopulation. Given this substantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decellularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve replacements by providing homologous, non-immunogenic, off-the-shelf replacement constructs. (C) 2013 Elsevier Ltd. All rights reserved.